Regulation of murine lymphokine production in vivo II. Dehydroepiandrosterone is a natural enhancer of interleukin 2 synthesis by helper T cells

Abstract

Dehydroepiandrosterone (DHEA) is an adrenal steroid hormone produced in abundance by humans and most other warm-blooded animals, is uniquely sulfated (DHEAS) prior to export into the plasma, and exhibits an age-related decline in production with progressive age. No major physiological functions have been ascribed to the activity of this steroid, although DHEA is known to serve as an intermediary in sex steroid synthesis. Studies on the effects of glucocorticoids (GCS) on the immune system led us to question whether DHEA had effects on the ability of activated lymphocytes to produce interleukin 2 (IL 2). We determined that (a) lymphocytes from DHEA- or DHEAS-treated mice consistently produced much greater levels of IL 2 than normals in response to stimulation, (b) direct lymphocyte exposure to DHEA at low doses (10(-10)-10(-7) M) caused an enhanced capacity to secrete IL 2 following activation, (c) IL 2 production by activated cloned T cell lines could be augmented by DHEA treatment, and (d) GCS-induced depressions in IL 2 synthesis by T cells or T cell clones could be overcome in vitro and in vivo by exposure to the effects of DHEA. These findings suggest that DHEA, presumably through receptor-mediated mechanisms similar to other types of steroid hormones, may represent a natural and important regulator of IL 2 production in both normal and pathologic conditions.

Regulation of murine lymphokine production in vivo. III. The lymphoid tissue microenvironment exerts regulatory influences over T helper cell function.

“…Our recent work with the normal androgen steroid DHEA established that this hormone had a strong positive influence on the ability of T cells to produce IL-2 after activation (18). DHEA represents the major adrenal steroid produced by humans between their second and fifth decades of life (14,16), and is uniquely sulfated to DHEA-sulfate before secretion into the plasma (29).…”

“…DHEA represents the major adrenal steroid produced by humans between their second and fifth decades of life (14,16), and is uniquely sulfated to DHEA-sulfate before secretion into the plasma (29). Unlike DHEA, DHEA-sulfate is incapable of affecting TCGF production by lymphocytes directly exposed to the hormone in vitro (18). Interestingly, DHEA was very effective in vivo in augmenting the capacity of isolated peripheral lymph node, spleen, and Peyer's patch lymphocytes to produce IL-2 after activation, while DHEA-sulfate was found to only be active on peripheral lymph node and spleen lymphocytes (Fig.…”

“…Studies have now determined that dehydroepiandrosterone (DHEA), the major androgen steroid hormone in humans (14)(15)(16)(17), is capable of enhancing the potential of murine T cells to produce IL-2 subsequent to appropriate activation (18). In addition to a direct effect on T cells in vitro, DHEA treatment ofnormal or GC-treated animals resulted in an enhanced capacity of their T cells to produce IL-2 in response to antigen or mitogen stimulation .…”

An open study of dehydroepiandrosterone in systemic lupus erythematosus

“…Decreased secretion of interleukin-2 (IL-2) has been reported in SLE, both in vitro and in vivo (16,17), and administration of IL-2 through gene transfer has been reported to ameliorate murine lupus (18). DHEA has been shown to increase secretion of IL-2 by stimulated T cells in both human (19) and murine (20) systems, and to normalize the excessive production of IL-4, IL-5, and IL-6 in aged mice (21). It is interesting that the latter cytokines all up-regulate B cell differentiation and/or antibody synthesis, and elevated levels of IL-6 have been reported in SLE (22).…”

Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus

“…Previous studies in animal models of SLE have demonstrated improvement with androgen administration, including DHEA (9)(10)(11)(12)(13)(14). In addition to serving as a precursor for other androgenic and estrogenic steroids (5), there is evidence that DHEA has an immunomodulatory role, including upregulation of interleukin-2 (IL-2) and down-regulation of IL-6 expression (9,(15)(16)(17), both of which have been reported to be abnormal in SLE (18)(19)(20).…”